Facile superhydrophobic modification on HPMC film using polydimethylsiloxane and starch granule coatings.

The excessive water sensitivity of hydroxypropyl methylcellulose (HPMC) films prevent them from being used extensively. In order to overcome this limitation, superhydrophobic HPMC films were meticulously crafted through the utilization of a composite of polydimethylsiloxane (PDMS) and ball-milled rice starch, corn starch, or potato starch (RS/CS/PS) for the coating process. Initially possessing hydrophilic properties, the HPMC Film (CA = 49.3 ± 1.8°) underwent a transformative hydrophobic conversion upon the application of PDMS, resulting in a static contact angle measuring up to 103.4 ± 2.0°. Notably, the synergistic combination of PDMS-coated HPMC with ball-milled starch demonstrated exceptional superhydrophobic attributes. Particularly, the treated HPMC-based film, specifically the HP-CS-2 h film, showcased an impressive contact angle of 170.5° alongside a minimal sliding angle of 5.2°. The impact of diverse starch types and the ball milling treatment on the PDMS/starch coatings and HPMC film was thoroughly examined using scanning electron microscopy (SEM), wide-angle X-ray diffraction (WAXS), and particle size analysis. These studies demonstrated that the low surface energy and roughness required for the creation of superhydrophobic HPMC-based films were imparted by the hierarchical structure formed by the application of PDMS/ball-milled starch. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Polydimethylsiloxane (PubChem CID: 24764); Hydroxypropyl methylcellulose (PubChem CID: 671); Ethyl acetate (PubChem CID: 8857).

Phase transforming in situ gels for sustained and controlled transmucosal drug delivery via the intravaginal route.

Direct, reliable, controlled, and sustained drug delivery to female reproductive tract (FRT) remains elusive, with conventional dosage forms falling way short of the mark, leading to premature leakage, erratic drug delivery, and loss of compliance. Historically, the intravaginal route remains underserved by the pharmaceutical sector. To comprehensively address this, we turned our focus to phase-transforming sol-gels, using poloxamers, a thermosensitive polymer and, doxycycline (as hyclate salt, DOXH) as our model agent given its potential use in sexually transmitted infections (STIs). We further enhanced mucoadhesiveness through screening of differing viscosity grade hydroxypropyl methyl celluloses (HPMCs). The optimised sol-gels remained gelled at body temperature (<37 °C) and were prepared in buffer aligned to vaginal cavity pH and osmolality. Lead formulations were progressed based on their ability to retain key rheological properties, and acidic pH in the presence of simulated vaginal fluid (SVF). From a shelf-life perspective, DOXH stability, gelation temperature (Tsol-gel), and pH to three months (2-8 °C) was attained. In summary, the meticulously engineered, phase-transforming sol-gels provided sustained mucoretention despite dilution by vaginal fluid, paving the way for localised antimicrobial drug delivery at concentrations that potentially far exceed the minimum inhibitory concentration (MIC) for target STI-causing bacteria of the FRT.

An empirical predictive model for determining the aqueous solubility of BCS class IV drugs in amorphous solid dispersions.

CONTEXT: Determining solubility of drugs is laborious and time-consuming process that may not yield meaningful results. Amorphous solid dispersion (ASD) is a widely used solubility enhancement technique. Predictive models could streamline this process and accelerate the development of oral drugs with improved aqueous solubilities. OBJECTIVE: This study aimed to develop a predictive model to estimate the solubility of a compound from the ASDs in polymer matrices. METHODS: ASDs of model drugs (acetazolamide, chlorothiazide, furosemide, hydrochlorothiazide, sulfamethoxazole) with model polymers (PVP, PVPVA, HPMC E5, Soluplus) and a surfactant (TPGS) were prepared using hotmelt process. The prepared ASDs were characterized using DSC, FTIR, and XRD. The aqueous solubility of the model drugs was determined using shake-flask method. Multiple linear regression was used to develop a predictive model to determine aqueous solubility using the molecular descriptors of the drug and polymer as predictor variables. The model was validated using Leave-One-Out Cross-Validation. RESULTS: The ASDs' drug components were identified as amorphous via DSC and XRD Studies. There were no significant chemical interactions between the model drugs and the polymers based on FTIR studies. The ASDs showed a significant (p < 0.05) improvement in solubility, ranging from a 3-fold to 118-fold, compared with the pure drug. The developed empirical model predicted the solubility of the model drugs from the ASDs containing model polymer matrices with an accuracy greater than 80%. CONCLUSION: The developed empirical model demonstrated robustness and predicted the aqueous solubility of model drugs from the ASDs of model polymer matrices with an accuracy greater than 80%.

Development of nanostructured environmentally responsive system containing hydroxypropyl methylcellulose for nose-to-brain administration of meloxicam.

The intranasal administration of drugs using environmentally responsive formulations, employing a combination of hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407), can result in release systems that may assist in the treatment of neurological diseases. Meloxicam, considered a potential adjuvant in the treatment of Alzheimer's disease, could be used in these platforms. The aim of this work was to develop a mucoadhesive, thermoresponsive, and nanostructured system containing HPMC for nose-to-brain administration of meloxicam. The initially selected systems were investigated for their rheological, mechanical, and micellar size characteristics. The systems were dilatant at 25 °C and pseudoplastic with a yield value at 37 °C, showing viscoelastic properties at both temperatures. The platform containing HPMC (0.1%, w/w) and P407 (17.5%, w/w) was selected and demonstrated good mucoadhesive properties, along with an appropriate in vitro release profile. HPMC could form a binary system with P407, displaying superior mucoadhesive and thermoresponsive properties for nose-to-brain meloxicam administration, indicating that the selected formulation is worthy of clinical studies.

In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid® 244FP-Based Ternary Solid Dispersion of Flurbiprofen.

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

The wound healing effect of polycaprolactone-chitosan scaffold coated with a gel containing Zataria multiflora Boiss. volatile oil nanoemulsions.

AIMS: Thymus plant is a very useful herbal medicine with various properties such as anti-inflammatory and antibacterial. Therefore, the properties of this plant have made this drug a suitable candidate for wound healing. In this study, hydroxypropyl methylcellulose (HPMC) gel containing Zataria multiflora volatile oil nanoemulsion (neZM) along with polycaprolactone/chitosan (PCL-CS) nanofibrous scaffold was used, and the effect of three experimental groups on the wound healing process was evaluated. The first group, HPMC gel containing neZM, the second group, PCL-CS nanofibers, and the third group, HPMC gel containing neZM and bandaged with PCL-CS nanofibers (PCL-CS/neZM). Wounds bandaged with common sterile gas were considered as control. METHODS: The nanoemulsion was synthesized by a spontaneous method and loaded into a hydroxypropyl methylcellulose (HPMC) gel. The DLS test investigated the size of these nanoemulsions. A PCL-CS nanofibrous scaffold was also synthesized by electrospinning method then SEM and contact angle tests investigated morphology and hydrophilicity/hydrophobicity of its surface. The animal study was performed on full-thickness skin wounds in rats, and the process of tissue regeneration in the experimental and control groups was evaluated by H&E and Masson's trichrome staining. RESULTS: The results showed that the nanoemulsion has a size of 225±9 nm and has an acceptable dispersion. The PCL-CS nanofibers synthesized by the electrospinning method also show non-beaded smooth fibers and due to the presence of chitosan with hydrophilic properties, have higher surface hydrophobicity than PCL fibers. The wound healing results show that the PCL-CS/neZM group significantly reduced the wound size compared to the other groups on the 7th, 14th, and 21st days. The histological results also show that the PCL-CS/neZM group could significantly reduce the parameters of edema, inflammation, and vascularity and increase the parameters of fibrosis, re-epithelialization, and collagen deposition compared to other groups on day 21. CONCLUSION: The results of this study show that the PCL-CS/neZM treatment can effectively improve wound healing.

Impact of drug load and polymer molecular weight on the 3D microstructure of printed tablets.

This study investigates the influence of drug load and polymer molecular weight on the structure of tablets three-dimensionally (3D) printed from the binary mixture of prednisolone and hydroxypropyl methylcellulose (HPMC). Three different HPMC grades, (AFFINISOLTM HPMC HME 15LV, 90 Da (HPMC 15LV); 100LV, 180 Da (HPMC 100LV); 4M, 500 Da (HPMC 4M)), which are suitable for hot-melt extrusion (HME), were used in this study. HME was used to fabricate feedstock material, i.e., filaments, at the lowest possible extrusion temperature. Filaments of the three HPMC grades were prepared to contain 2.5, 5, 10 and 20 % (w/w) prednisolone. The thermal degradation of the filaments was studied with thermogravimetric analysis, while solid-state properties of the drug-loaded filaments were assessed with the use of X-ray powder diffraction. Prednisolone in the freshly extruded filaments was determined to be amorphous for drug loads up to 10%. It remained physically stable for at least 6 months of storage, except for the filament containing 10% drug with HPMC 15LV, where recrystallization of prednisolone was detected. Fused deposition modeling was utilized to print honeycomb-shaped tablets from the HME filaments of HPMC 15LV and 100LV. The structural characteristics of the tablets were evaluated using X-ray microcomputed tomography, specifically porosity and size of structural elements were investigated. The tablets printed from HPMC 15LV possessed in general lower total porosity and pores of smaller size than tablets printed from the HPMC 100LV. The studied drug loads were shown to have minor effect on the total porosity of the tablets, though the lower the drug load was, the higher the variance of porosity along the height of the tablet was observed. It was found that tablets printed with HPMC 15LV showed higher structural similarity with the virtually designed model than tablets printed from HPMC 100LV. These findings highlight the relevance of the drug load and polymer molecular weight on the microstructure and structural properties of 3D printed tablets.

Clinical evaluation of liposome-based gel formulation containing glycolic acid for the treatment of photodamaged skin.

Background: Long contact of UV causes skin damage. Glycolic acid (GA) as an alpha hydroxy acid is used to treat photodamaged skin. However, GA leads to side effects including; burning, erythema and peeling.Purpose: The aim of this study was to develop a controlled delivery systems loading GA in order to increasing its efficacy and lowering its side effects.Methods: Liposomes were evaluated for encapsulation efficiency, size and morphology. Optimized formulation was dispersed in HPMC gel bases and drug release kinetics were also studied. Clinical efficacy and safety of GA-loaded liposomal gel and GA gel formulation were evaluated in patients with photodamaged skin.Results: The EE% and average particle size of liposomes were 64 ±2.1 % and 317±3.6 nm, respectively. SEM image showed that liposomes were spherical in shape. In vitro release kinetics of GA from both formulations followed Weibull model. Clinical evaluation revealed that GA-loaded liposomal gel was more effective than GA gel formulation. Treatment with GA-loaded liposomal gel resulted in a statistically significant reduction in the scores of hyperpigmentation, fine wrinkling and lentigines. Moreover, liposomal gel formulation was able to minimize side effects of GA.Conclusion: According to the obtained results, the liposome-based gel formulation can be used as potential drug delivery system to enhance permeation of GA through skin layers and also reduce its side effects.

Successful cryopreservation in biodegradable containers of sperm from aquaculture Mediterranean fishes.

We aimed to evaluate the efficiency of hard-gelatin and hard-hydroxypropyl methylcellulose (HPMC) capsules as biodegradable alternative containers to plastic straws in European eel (Anguilla anguilla), gilthead seabream (Sparus aurata) and European sea bass (Dicentrarchus labrax) sperm cryopreservation. Sperm samples from each European eel (n = 12) were diluted 1:8:1 (sperm: extender P1+5 % egg yolk: methanol). Gilthead seabream (n = 12) samples were individually diluted in a cryoprotectant solution of 5 % Me2SO + NaCl 1 % plus BSA (10 mg mL-1) at a ratio of 1:6 (sperm: cryoprotectant solution). European sea bass (n = 10) sperm from each male was diluted in non-activating medium (NAM) at a ratio of 1:5.7 (sperm: NAM), and 5 % of Me2SO was added. The diluted European eel and sea bass sperm aliquots (0.5 mL) were individually filled in plastic straws (0.5 mL), hard-gelatin, and HPMC capsules (0.68 mL). Gilthead seabream diluted sperm (0.25 mL) were filled in plastic straws (0.25 mL) and identical capsules described. All samples were frozen in liquid nitrogen vapor and stored in a liquid nitrogen tank. Sperm kinetic parameters were evaluated by CASA-Mot software. Sperm membrane integrity was performed using a Live and Dead KIT and an epifluorescence microscope. To quantify DNA damage, the alkaline comet assay was performed and TailDNA (TD-%) and Olive Tail Moment (OTM) were evaluated by CaspLab software. Sperm cryopreservation of the three Mediterranean species in straws, gelatin, or HPMC capsules reduced the kinetic parameters and cell membrane integrity. Generally, the post-thawing samples cryopreserved in straws and capsules did not differ for the kinetic parameters and cell membrane integrity, except for European sea bass sperm, where the samples stored in gelatin capsules showed higher velocities (VCL - 100; VSL - 76; VAP - 90 µm s-1) than the sperm stored in HPMC capsules (VCL - 87; VSL - 59; VAP - 73 µm s-1). The cryopreservation process did not damage the sperm DNA of European eel and European sea bass, regardless of the containers used. On the other hand, gilthead seabream sperm cryopreserved in gelatin (TD - 9.8 %; OTM - 9.7) and HPMC (TD - 11.1 %; OTM - 11.2) capsules showed higher DNA damage than fresh samples (TD - 3.6 %; OTM - 2.7) and the sperm stored in straws (TD - 4.4 %; OTM - 5.2). The hard-gelatin and HPMC biodegradable capsules can be used as an alternative to straws for European eel, gilthead seabream, and European sea bass sperm cryopreservation.

Development of Sustained Release System Based on High Water-Absorbable Gel Formation Using Croscarmellose Sodium, Alkaline Excipients and HPMC (ACSH SR System); Novel Application of Croscarmellose Sodium as a Gel Former.

PURPOSE: Croscarmellose sodium, generally used as a superdisintegrant in pharmaceutical formulations, is hydrolyzed to form the gel structure under basic pH conditions. Utilizing this property of croscarmellose sodium, we developed a novel sustained release (SR) system. METHODS: Immediate release (IR) and SR tablets containing croscarmellose sodium, alkaline excipients and/or hydroxypropyl methylcellulose (HPMC) were prepared and examined for wet strength and in vitro drug release behavior. In vivo oral drug absorption was evaluated for IR tablets, HPMC tablets and our novel SR tablets in fasted Beagle dogs. RESULTS: To form the gel structure even under the physiological condition, alkaline excipients were added into the formulation containing croscarmellose sodium. Furthermore, HPMC was used to make the gel structure strong enough against mechanical destructive forces. The novel alkalized croscarmellose sodium-HPMC (ACSH) SR tablet, consisting of croscarmellose sodium, alkaline excipients, and HPMC, successfully sustained the release of acetaminophen, ibuprofen, or nicardipine hydrochloride, compared with the IR tablets. The ACSH SR system provided a better release of acetaminophen than the HPMC tablet without croscarmellose sodium in the release study using a small volume of liquid, suggesting that substantial release and subsequent absorption would be expected in the distal intestinal segments after oral dosing. The in vivo oral absorption study revealed that the ACSH SR system successfully suppressed and prolonged the plasma concentrations of acetaminophen. CONCLUSION: This novel ACSH SR system prepared with croscarmellose sodium, alkaline excipients, and HPMC, would be a promising SR formulation for enabling substantial drug absorption in the distal intestinal segments.

The Preparation and Evaluation of Cyanocobalamin Mucoadhesive Sublingual Tablets.

Cobalamin (vitamin B12), an essential vitamin with low oral bioavailability, plays a vital role in cellular functions. This research aimed to enhance the absorption of vitamin B12 using sublingual mucoadhesive tablets by increasing the residence time of the drug at the administration site. This research involved the preparation of different 50 mg placebo formulas using different methods. Formulas with disintegration times less than one minute and appropriate physical characteristics were incorporated into 1 mg of cyanocobalamin (S1-S20) using the direct compression method. The tablets obtained were evaluated ex vivo for residence time, and only those remaining for >15 min were included. The final formulas (S5, S8, S11, and S20) were evaluated in several ways, including pre- and post-compression, drug content, mucoadhesive strength, dissolution, and Permeapad® permeation test employed in the Franz diffusion cell. After conducting the evaluation, formula S11 (Eudragit L100-55) emerged as the most favorable formulation. It exhibited a mucoadhesive residence time of 118.2 ± 2.89 min, required a detachment force of 26 ± 1 g, maintained a drug content of 99.124 ± 0.001699%, and achieved a 76.85% drug release over 22 h, fitting well with the Peppas-Sahlin kinetic model (R2: 0.9949). This suggests that the drug release process encompasses the Fickian and non-Fickian kinetic mechanisms. Furthermore, Eudragit L100-55 demonstrated the highest permeability, boasting a flux value of 6.387 ± 1.860 µg/h/cm2; over 6 h. These findings indicate that including this polymer in the formulation leads to an improved residence time, which positively impacts bioavailability.

Novel Sprayable Thermosensitive Benzydamine Hydrogels for Topical Application: Development, Characterization, and In Vitro Biological Activities.

Benzydamine hydrochloride (BZD) having analgesic, anesthetic, and anti-inflammatory effects is used orally or topically in the treatment of disorders such as joint inflammation and muscle pain. Within the scope of this study, sprayable thermosensitive BZD hydrogels were developed using thermoresponsive poloxamers to avoid systemic side effects and to provide better compliance for topical administration. Also, hydroxypropyl methyl cellulose (HPMC) was employed to improve the mechanical strength and bioadhesive properties of the hydrogel. The addition of BZD generally decreased the viscosity of the formulations (p < 0.05), while increasing the gelation temperature (p < 0.05). The formulations that did not have any clogs or leaks in the nozzle of the bottle during the spraying process were considered lead formulations. To spray the formulations easily, it was found that the viscosity at RT should be less than 200 mPa·s, and their gelation temperature should be between 26 and 34°C. Increasing HPMC and poloxamer improved bioadhesion. The amount of HPMC and poloxamers did not cause a significant change in the release characteristics of the formulations (p > 0.05); the release profiles of BZD from the formulations were similar according to model-independent kinetic (f2 > 50). HPMC and poloxamers had important roles in the accumulation of BZD in the skin. In vitro biological activity studies demonstrated that the formulations presented their anti-inflammatory activity with TNF-α inhibition but did not have any effect on the inhibition of COX enzymes as expected. As a result, thermosensitive hydrogels containing BZD might be an appropriate alternative, providing an advantage in terms of easier application compared to conventional gels.

Formulation Of Benzoyl Peroxide Microsponge-Based Transdermal Gel For Acne Infection And Its Evaluation.

BACKGROUND: Benzoyl peroxide is a peroxide with antibacterial, irritating, keratolytic, comedolytic, and anti-inflammatory properties. When benzoyl peroxide is applied topically, it breaks down and releases oxygen, which kills the germs of Propionibacterium acnes. Benzoyl peroxide's irritating impact causes an increase in epithelial cell turnover, which causes the skin to peel and aids in the healing of comedones. Treatment for acne vulgaris involves the use of benzoyl peroxide. OBJECTIVE: The research is aimed at studying the formulation of Microsponge gel preparation of benzoyl peroxide by using Carbopol 934 as a gelling agent and evaluation of microsponge gel formulation for its physicochemical properties. METHODS: Microsponges of Anti-acne agent benzoyl peroxide drug were prepared by quasi-emulsion method, and in-vitro drug release using a suitable membrane model using a simple diffusion cell. RESULT: Prior to drying, the microsponge was filtered and rinsed using distilled water. Formulation containing benzoyl peroxide and Eudragit RS100 with a ratio of 1:4 showed a high 87.5% drug content and 78.20 % yield. The drug content of the microsponge gel was found to be 84%. Microbiological study on S. aureus was conducted by the cylinder cup method and found good results. The in-vitro diffusion of microsponge formulations was sustained for 8 hours. The drug release rate for Eudragit RS-100 was reported to be 88.87% after 8 hours based on the polymer: drug ratio (4:1). CONCLUSION: The quasi-emulsion solvent diffusion method was used to successfully prepare benzoyl peroxide microsponges using Eudragit RS100, Ethyl Cellulose, and HPMC K4M as polymers. The formulations with the highest medication concentration were made with the porous polymer Eudragit RS100.

Halloysite nanotubes-cellulose ether based biocomposite matrix, a potential sustained release system for BCS class I drug verapamil hydrochloride: Compression characterization, in-vitro release kinetics, and in-vivo mechanistic physiologically based pharmacokinetic modeling studies.

This study investigated the ability of natural nanotubular clay mineral (Halloysite) and cellulose ether based biocomposite matrix as a controlled release agent for Verapamil HCl (BCS Class-I). Drug-loaded halloysite was prepared and tablet formulations were designed by varying amount of hydroxy propyl methyl cellulose (HPMC K4M). Physical characterization was carried out using SEM, FTIR, and DSC. Tabletability profiles were evaluated using USP1062 guidelines. Drug release kinetics were studied, and physiologically based pharmacokinetic (PBPK) modeling was performed. Compressed tablets possess satisfactory yield pressure of 625 MPa with adequate hardness and disintegration within 30 min. The initial release of the drug was due to surface drug on tablets, while the prolonged release at later time points (around 80 % drug release at 12 h) were due to halloysite loading. The FTIR spectra exhibited electrostatic attraction between the positively charged drug and the negatively charged Si-O-Si functional group of halloysite, while the thermogram showed Verapamil HCl melting point at ~146 °C with enthalpy change of -126.82 J/g. PBPK modeling exhibited PK parameters of optimized matrix formulation (VER-HNT3%) comparable to in vivo data. The study effectively demonstrated the potential of prepared biocomposite matrix as a commercially viable oral release modifying agent for highly soluble drugs.

Tablet Geometry Effect on the Drug Release Profile from a Hydrogel-Based Drug Delivery System.

In order to achieve the optimal level of effectiveness and safety of drugs, it is necessary to control the drug release rate. Therefore, it is important to discover the factors affecting release profile from a drug delivery system. Geometry is one of these effective factors for a tablet-shaped drug delivery system. In this study, an attempt has been made to answer a general question of how the geometry of a tablet can affect the drug release profile. For this purpose, the drug release process of theophylline from two hundred HPMC-based tablets, which are categorized into eight groups of common geometries in the production of oral tablets, was simulated using finite element analysis. The analysis of the results of these simulations was carried out using statistical methods including partial least squares regression and ANOVA tests. The results showed that it is possible to predict the drug release profile by knowing the geometry type and dimensions of a tablet without performing numerous dissolution tests. Another result was that, although in many previous studies the difference in the drug release profile from several tablets with different geometries was interpreted only by variables related to the surface, the results showed that regardless of the type of geometry and its dimensions, it is not possible to have an accurate prediction of the drug release profile. Also, the results showed that without any change in the dose of the drug and the ingredients of the tablet and only because of the difference in geometry type, the tablets significantly differ in release profile. This occurred in such a way that, for example, the release time of the entire drug mass from two tablets with the same mass and materials but different geometries can be different by about seven times.

Increased bioavailability of a P-gp substrate: Co-release of etoposide and zosuquidar from amorphous solid dispersions.

P-glycoprotein (P-gp) inhibitors, like zosuquidar, partly increase oral bioavailability of P-gp substrates, such as etoposide. Here, it was hypothesised that co-release of etoposide and zosuquidar from amorphous solid dispersions (ASDs) may further increase oral etoposide bioavailability. This was envisioned through simultaneous co-release and subsequent spatiotemporal association of etoposide and zosuquidar in the small intestinal lumen. To further achieve this, ASDs of etoposide and zosuquidar in polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) 5, and HPMC 4 k were prepared by freeze-drying. From these ASDs, etoposide release was fastest from PVP, then HPMC 5 and slowest from HPMC 4. Release from PVP and HPMC5 resulted in stable supersaturations of etoposide. In transcellular permeability studies across MDCKII-MDR1 cell monolayers, the accumulated amount of etoposide increased 3.7-4.9-fold from amorphous etoposide or when incorporated into PVP- or HPMC 5-based ASDs, compared to crystalline etoposide. In vivo, the oral bioavailability in Sprague Dawley rats increased from 1.0 to 2.4-3.4 %, when etoposide was administered as amorphous drug or in ASDs. However, when etoposide and zosuquidar were co-administered, the oral bioavailability increased further to 8.2-18 %. Interestingly, a distinct increase in oral etoposide bioavailability to 26 % was observed when etoposide and zosuquidar were co-administration in HPMC5-based ASDs. The supersaturation of etoposide as well as the simultaneous co-release of etoposide and zosuquidar in the small intestinal lumen may explain the observed bioavailability increase. Overall, this study suggested that simultaneous co-release of an amorphous P-gp substrate and inhibitor may be a novel and viable formulation strategy to increase the bioavailability P-gp substrates.

Enhancing the dissolution rate of poorly soluble drug Febuxostat using spray dried amorphous solid dispersion technique / Mejora de la tasa de disolución del fármaco poco soluble Febuxostat utilizando la técnica de dispersión de sólido amorfo secado por aspersión

Introducción: El febuxostat pertenece a los fármacos clase II del Sistema de Clasificación Biofarmacéutica, los cuales presentan baja solubilidad y alta permeabilidad. La dispersión sólida amorfa es una de las técnicas que pueden ser útiles para mejorar la solubilidad y las características del polvo. Objetivo: optimizar la concentración de polímeros hidrofílicos e hidrofóbicos para mejorar la velocidad de disolución y la solubilidad de las tabletas de febuxostat. Métodos: La dispersión sólida amorfa de febuxostat se preparó mediante el método de secado por aspersión utilizando Kolliphor P237 (1:2). Esta dispersión sólida amorfa se utilizó además para comprimir el comprimido. Para mejorar la solubilidad y la tasa de disolución, se aplicó un diseño factorial completo para optimizar la concentración crítica de KollidonSR e hidroxi propil metil celulosa (HPMC K4M). Los comprimidos preparados se caracterizaron por parámetros de precompresión y poscompresión. Resultados: La velocidad de liberación del fármaco se mantuvo mediante la formulación de una técnica de dispersión sólida amorfa. Se encontró que el lote optimizado (FSRT-OB) era apto para la liberación promedio del 93,30 % del fármaco en forma de liberación sostenida hasta 12 horas. Los datos de la cinética de liberación sugieren que la liberación del fármaco estuvo controlada por una combinación de mecanismo de relajación de cadena y difusión. Se encontró que la concentración optimizada para Kollidon SR y HPMC K4M era 38,50 % y 7,72 % respectivamente. Conclusión: La técnica de dispersión sólida amorfa es útil para mejorar la solubilidad, la velocidad de disolución y la biodisponibilidad de la tableta de Febuxostat. (AU)

Introduction: Febuxostat belongs to Biopharmaceutical classification system (BCS) class II drugs, which have low solubility and high permeability. Amorphous solid dispersion is one of the techniques which can be useful to improve solubility and powder characteristics. Objective: To optimize the concentration of hydrophilic and hydrophobic polymers to improve the dissolution rate and solubility of febuxostat tablets. Methods: The amorphous solid dispersion of febuxostat was prepared by spray drying method using Kolliphor P237 (1:2). This amorphous solid dispersion was further used to compress the tablet. To improve solubility and dissolu-tion rate, a full factorial design was applied to optimize the critical concentration of Kollidon SR and hydroxypropyl methyl cellulose (HPMC K4M). The prepared tablets were characterized by pre-compression and post-compression parameters. Result: The rate of drug release was sustained by formulating an amorphous solid dispersion technique. The optimized batch (FSRT-OB) was found to be fit for release average 93.30 % of the drug in sustain release manner up to 12hrs. The release kinetic data suggests that the drug release was controlled by combination of diffusion and chain relaxation mechanism. The optimized concentration for Kollidon SR and HPMC K4Mwas found to be 38.50 % and 7.72 % respectively. Conclusion: Amorphous solid dispersion technique is useful to enhance solubility, dissolution rate, and bioavail-ability of the Febuxostat tablet. (AU)

Triamcinolone acetonide release modelling from novel bilayer mucoadhesive films: an in vitro study.

OBJECTIVES: Recurrent aphthous stomatitis (RAS) is a painful disorder that commonly appears as ulcers on the oral mucosa, lasting ∼two weeks (minor) to months (major and herpetiform). Current treatment often necessitates the use of topical steroids in the form of pastes, mouthwashes, or gels, but these forms are often ineffective due to inadequate drug contact time with the ulcers. In this study, the performance of novel bilayer mucoadhesive buccal films loaded with triamcinolone acetonide (TA) has been evaluated for targeted drug delivery. METHODS: Experimental mucoadhesive films of hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol (PVA), and polyvinyl pyrrolidone (PVP) were prepared by the solvent casting method, and ethyl cellulose (EC) was applied as the backing layer. The films were characterized for their physical properties, including swelling index (SI), folding endurance, adhesion force with porcine buccal mucosa, residence time and in-vitro drug release. RESULTS: The data showed that the films were flexible with folding endurance> 300 times. With porcine buccal mucosa i) suitable adhesion forces were obtained (between 2.72 and 4.03 N), ii) residence times of> 24 h, and iii) surface pH between 6.8 and 7.1 indicating they would be non-irritant. All films released 100% TA over 6 h, but with varying profiles. The release of TA (over 6 h) from PVP-free films followed Fickian diffusion kinetics (diffusion-controlled release of drug), whereas the mechanism of release from PVP-containing films was found to be a superposition of diffusion-controlled and erosion-controlled release (anomalous). SIGNIFICANCE: The developed films hold great promise for potentially treating RAS and other oral conditions.

Comparison of topographic outcomes between HPMC based and vitamin E TPGS based riboflavin solutions after corneal cross-linking.

PURPOSE: To compare the visual and topographic results between patients who underwent epithelium-off cross-linking using riboflavin solutions compounds hydroxypropyl methylcellulose (HPMC) 1.1% and D-alpha-tocopheryl polyethylene-glycol 1000 succinate (VE-TPGS). METHODS: In this study, 37 eyes treated with HPMC and 29 eyes treated with VE-TPGS were evaluated retrospectively. Spherical equivalent (SE), refractive cylinder, corrected distance visual acuity tests (CDVA), corneal topography indices (flat and steep meridians' keratometry (K1 and K2)), maximum keratometry (K max), central, thinnest, and apical corneal thicknesses, the front and back keratoconus vertex index (KVf, KVb), and the surface asymmetry index of the front and back surface (SIf, SIb), and endothelial cell density were compared at baseline and postoperative follow-up visits (1, 3, 6, and 12months). RESULTS: At the end of the 12th-month, K1, K2, and Kmax were decreased in both groups. In comparison to baseline, there was a decline in the HPMC group in the 3rd- month Kmax change, an increase was observed in the VE-TPGS group. In the 12th-month KVb change, an increase was observed in the HPMC group compared to the baseline, while a decrease was observed in the VE-TPGS group. The other parameters did not show a statistically significant difference between the groups (p > 0.05). CONCLUSION: At the end of 12 months, both riboflavins were effective in stopping the progression of keratoconus and were safe for endothelium. Although both riboflavins provide a decrease in keratometry values, it can be said that VE-TPGS is superior to HPMC in correcting the ectasia on the posterior corneal surface.

Comparative Study of Selected Excipients' Influence on Carvedilol Release from Hypromellose Matrix Tablets.

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within the same experimental setup, including different grades of excipients. Compression mixtures were directly compressed using constant compression speed and main compression force. LOESS modelling was used for a detailed comparison of carvedilol release profiles via estimating burst release, lag time, and times at which a certain % of carvedilol was released from the tablets. The overall similarity between obtained carvedilol release profiles was estimated using the bootstrapped similarity factor (f2). In the group of water-soluble carvedilol release modifying excipients, which produced relatively fast carvedilol release profiles, POLYOXᵀᴹ WSR N-80 and Polyglykol® 8000 P demonstrated the best carvedilol release control, and in the group of water-insoluble carvedilol release modifying excipients, which produced relatively slow carvedilol release profiles, AVICEL® PH-102 and AVICEL® PH-200 performed best.